The evolution of gene expression and binding specificity of the largest transcription factor family in primates
Bibliographic record
Abstract
The KRAB-containing zinc finger (KRAB-ZF) proteins represent the largest family of transcription factors (TFs) in humans, yet for the great majority, their function and specific genomic target remain unknown. However, it has been shown that a large fraction of these genes arose from segmental duplications, and that they have expanded in gene and zinc finger number throughout vertebrate evolution. To determine whether this expansion is linked to selective pressures acting on different domains, we have manually curated all KRAB-ZF genes present in the human genome together with their orthologous genes in three closely related species and assessed the evolutionary forces acting at the sequence level as well as on their expression profiles. We provide evidence that KRAB-ZFs can be separated into two categories according to the polymorphism present in their DNA-contacting residues. Those carrying a nonsynonymous single nucleotide polymorphism (SNP) in their DNA-contacting amino acids exhibit significantly reduced expression in all tissues, have emerged in a recent lineage, and seem to be less strongly constrained evolutionarily than those without such a polymorphism. This work provides evidence for a link between age of the TF, as well as polymorphism in their DNA-contacting residues and expression levels-both of which may be jointly affected by selection.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".